DESCRIPTION: (Applicant's Description) The Clinical Trial Program of the CATBRM has responsibility for carrying out clinical trials utilizing recombinant tumor vaccines in patients with cancer. The emphasis of the trials is to utilize immunization strategies employing defined human tumor-associated antigens with utilization of specific tumor immune responses as intermediate markers in these phase I or II trials. Patients with low tumor burdens will be a primary objective to enhance the likelihood of induction of immune response to autologous tumor antigens. The program is currently carrying out a phase Ib trial of recombinant vaccinia-carcinoembryonic antigen (CEA) immunization in resected Dukes' C colorectal cancer patients and a phase I trial of baculovirus recombinant CEA protein immunization in hormone responsive metastatic breast cancer patients. This competitive renewal proposes new clinical trials using polynucleotide (plasmid DNA) immunization with a dual expressing plasmid encoding CEA and hepatitis B surface antigen (HBsAg). The first trial will be a phase I study in patients with metastatic colorectal cancer to examine increasing single and multiple dose schedules as regards toxicity and/or induction of immune response to CEA or HBsAg. The second trial will utilize an optimal dose/schedule of the same polynucleotide vaccine in patients with resected Dukes' C colorectal cancer to establish whether the regimen can induce significant CEA specific immune responses in at least 50 percent of patients. Patients will be, monitored for CEA-specific cellular immune responses (delayed hypersensitivity skin tests, T cell lymphocyte proliferation and lymphokine release profiles and cytolytic T cell precursors) as well as CEA-specific antibody assays. Immune response to HBsAg will provide an internal positive control for immune response to a non-self antigen. Confirmation of a high rate of CEA immune response induction would provide the rationale for phase III efficacy trials in the setting of adjuvant therapy for resected Dukes' B and C colorectal cancer (adjuvant trials).